Type IV pili-independent photocurrent production by the cyanobacterium Synechocystis sp. PCC 6803

Biophotovoltaic devices utilize photosynthetic organisms such as the model cyanobacterium Synechocystis sp. PCC 6803 (Synechocystis) to generate current for power or hydrogen production from light. These devices have been improved by both architecture engineering and genetic engineering of the phototrophic organism. However, genetic approaches are limited by lack of understanding of cellular mechanisms of electron transfer from internal metabolism to the cell exterior. Type IV pili have been implicated in extracellular electron transfer (EET) in some species of heterotrophic bacteria. Furthermore, conductive cell surface filaments have been reported for cyanobacteria, including Synechocystis. However, it remains unclear whether these filaments are type IV pili and whether they are involved in EET. Herein, a mediatorless electrochemical setup is used to compare the electrogenic output of wild-type Synechocystis to that of a ΔpilD mutant that cannot produce type IV pili. No differences in photocurrent, i.e., current in response to illumination, are detectable. Furthermore, measurements of individual pili using conductive atomic force microscopy indicate these structures are not conductive. These results suggest that pili are not required for EET by Synechocystis, supporting a role for shuttling of electrons via soluble redox mediators or direct interactions between the cell surface and extracellular substrates

A common classification framework for neuroendocrine neoplasms: an International Agency for Research on Cancer (IARC) and World Health Organization (WHO) expert consensus proposal.

The classification of neuroendocrine neoplasms (NENs) differs between organ systems and currently causes considerable confusion. A uniform classification framework for NENs at any anatomical location may reduce inconsistencies and contradictions among the various systems currently in use. The classification suggested here is intended to allow pathologists and clinicians to manage their patients with NENs consistently, while acknowledging organ-specific differences in classification criteria, tumor biology, and prognostic factors. The classification suggested is based on a consensus conference held at the International Agency for Research on Cancer (IARC) in November 2017 and subsequent discussion with additional experts. The key feature of the new classification is a distinction between differentiated neuroendocrine tumors (NETs), also designated carcinoid tumors in some systems, and poorly differentiated NECs, as they both share common expression of neuroendocrine markers. This dichotomous morphological subdivision into NETs and NECs is supported by genetic evidence at specific anatomic sites as well as clinical, epidemiologic, histologic, and prognostic differences. In many organ systems, NETs are graded as G1, G2, or G3 based on mitotic count and/or Ki-67 labeling index, and/or the presence of necrosis; NECs are considered high grade by definition. We believe this conceptual approach can form the basis for the next generation of NEN classifications and will allow more consistent taxonomy to understand how neoplasms from different organ systems inter-relate clinically and genetically

World Health Organization 4th edition of head and neck tumor classification: insight into the consequential modifications.

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Salivary flow rates measured during radiation therapy in head and neck cancer patients: A pilot study assessing salivary sediment formation

Statement of problem: Xerostomia often occurs in patients being managed for head and neck cancer who receive radiation therapy. Although accurate salivary sampling can be therapeutically important to measure during radiation, sampling errors can occur because of salivary sediments. Determining the impact that salivary sediments have on measured salivary flow rates during radiation is important for management of patients. Purpose: The purpose of this study was to assess the magnitude of error associated with the inclusion of nonsalivary components (sediment) in the calculation of whole stimulated saliva flow rates prior to and during radiation therapy (SS and SSR) in patients with head and neck cancer. Material and methods: Whole paraffin-stimulated saliva was collected in large-mouth centrifuge tubes from 20 patients with head and neck cancer prior to and during the third week of radiation therapy. Gravimetric methods were used to calculate the flow rates at g/5 min. After centrifugation, supernatant saliva was removed and the sediment was oven-dried to remove residual moisture. Sediment weight was subtracted from the original weight of saliva specimens and flow rates were recalculated. Means and standard deviations were determined and flow rate differences before (BC) and after (AC) sediment correction were evaluated statistically with the paired t test (α=.05). A nonparametric analysis of the flow rate data with the Wilcoxon matched-pairs signed-ranks test was also used to examine the magnitude and direction of the intrapair (BC-AC) differences (α=.05). Results: On average, salivary sediment contributed less than 1% of the total uncorrected weight of saliva prior to radiation therapy. In specimens collected during radiation therapy, sediment contributed an average of 14% of the total uncorrected weight and as high as 95.4% in 1 patient. Sediment percentages were 20% and higher in 4 patients. In the Wilcoxon analysis, 19 out of 20 paired BC and AC flow rates were higher in the BC group in the SS and SSR samples. Conclusions: The error associated with the inclusion of salivary sediment in the calculation of saliva flow rates prior to radiation treatment was small, but statistically significant. The magnitude of the sediment effect was more pronounced in specimens taken during radiotherapy and was significant, as determined by the Wilcoxon test, but the mean paired differences were not significantly different according to the t test. (J Prosthet Dent 2008;100:142-146). © 2008 The Editorial Council of the Journal of Prosthetic Dentistry

A miRNA signature associated with human metastatic medullary thyroid carcinoma

MicroRNAs (miRNAs) represent a class of small, non-coding RNAs that control gene expression by targeting mRNA and triggering either translational repression or RNA degradation. The objective of our study was to evaluate the involvement of miRNAs in human medullary thyroid carcinoma (MTC) and to identify the markers of metastatic cells and aggressive tumour behaviour. Using matched primary and metastatic tumour samples, we identified a subset of miRNAs aberrantly regulated in metastatic MTC. Deregulated miRNAs were confirmed by quantitative real-time PCR and validated by in situ hybridisation on a large independent set of primary and metastatic MTC samples. Our results uncovered ten miRNAs that were significantly expressed and deregulated in metastatic tumours: miR-10a, miR-200b/-200c, miR-7 and miR-29c were down-regulated and miR-130a, miR-138, miR-193a-3p, miR-373 and miR-498 were up-regulated. Bioinformatic approaches revealed potential miRNA targets and signals involved in metastatic MTC pathways. Migration, proliferation and invasion assays were performed in cell lines treated with miR-200 antagomirs to ascertain a direct role for this miRNA in MTC tumourigenesis. We show that the members of miR-200 family regulate the expression of E-cadherin by directly targeting ZEB1 and ZEB2 mRNA and through the enhanced expression of tumour growth factor β (TGFβ)-2 and TGFβ-1. Overall, the treated cells shifted to a mesenchymal phenotype, thereby acquiring an aggressive phenotype with increased motility and invasion. Our data identify a robust miRNA signature associated with metastatic MTC and distinct biological processes, e.g., TGFβ signalling pathway, providing new potential insights into the mechanisms of MTC metastasis

Alterations associated with androgen receptor gene activation in salivary duct carcinoma of both sexes : potential therapeutic ramifications

Purpose: To investigate the molecular events associated with the activation of androgen receptor (AR) as a potential therapeutic target in patients with salivary duct carcinoma (SDC). Experimental Design: Comprehensive molecular and expression analysis of the AR gene in 35 tumor specimens (20 males and 15 females) and cell lines derived from SDC using Western blotting and RT-PCR, FISH analysis, and DNA sequencing was conducted. In vitro and in vivo animal studies were also performed. Results: AR expression was detected in 70% of the tumors and was mainly nuclear and homogenous in both male and female SDCs, although variable cytoplasmic and/or nuclear localization was also found. We report the identification of ligand-independent AR splice variants, mutations, and extra AR gene copy in primary untreated SDC tumors. In contrast to prostate cancer, no AR gene amplification was observed. In vitro knockdown of AR in a female derived SDC cell line revealed marked growth inhibition in culture and in vivo androgen-independent tumor growth. Conclusions: Our study provides new detailed information on the molecular and structural alterations associated with AR gene activation in SDC and sheds more light on the putative functional role of AR in SDC cells. On the basis of these data, we propose that patients with SDC (male and female) can be stratified for hormone-based therapy in future clinical trials